Oligodendrocytes and REM sleep

[pairOdime]

It certainly seems likely that cerebral hypoperfusion due to CCSVI would have a negative impact on the ability to obtain REM stage sleep. The reduction in sufficient oxygen, glucose, various hormones, and CSF flow due to CCSVI could certainly help explain the impairment from a human perspective.

http://www.sciencedaily.com/releases/20 ... 193807.htm

In the current study, Chiara Cirelli, MD, PhD, and colleagues at the University of Wisconsin, Madison, measured gene activity in oligodendrocytes from mice that slept or were forced to stay awake. The group found that genes promoting myelin formation were turned on during sleep. In contrast, the genes implicated in cell death and the cellular stress response were turned on when the animals stayed awake.

"These findings hint at how sleep or lack of sleep might repair or damage the brain," said Mehdi Tafti, PhD, who studies sleep at the University of Lausanne in Switzerland and was not involved with this study.

Additional analysis revealed that the reproduction of oligodendrocyte precursor cells (OPCs) -- cells that become oligodendrocytes -- doubles during sleep, particularly during rapid eye movement (REM), which is associated with dreaming.

See link at the top for full article.

[cheerleader]

Absolutely, Pair! This sure would explain impairment in the CCSVI paradigm.

OPCs need O2--in fact, myelin is especially susceptable to hypoperfusion and ischemia.
http://www.sciencedirect.com/science/ar ... 4800000757

Here's part of a note I wrote for Facebook in 2010 on REM sleep and CCSVI --
another three years have passed since I wrote this, and he's still sleeping soundly, dreaming, and his brain continues to heal on MRI.

One of the most profound, although seemingly minor changes for my husband, now 18 months since his angioplasty--has been the return of dreaming. After his procedure, he would wake up in the morning and recount for me his vivid dream from the night before. It was so strange to us...he realized that for several years, he couldn't remember his dreams. When I went to the CCSVI international symposium in Bologna last year, Dr. Salvi got up and spoke about the changes in his patients after angioplasty. And one of the global differences his patients noted was deeper, more restful sleep...and the return of dreams. He had a wonderful illustration that came on the screen during his power-point... a cartoon of a person deeply sleeping, smiling, with a colorful dream bubble over their head. I almost leapt out of my seat. "That's happened to Jeff!" I whisper/exclaimed to Dr. Dake, seated on my left. "He's dreaming again."

Now, I read time and time again from patients and their caregivers about the return of deep, restful sleep and dreaming. I realize that dreaming might not seem important in the grand scheme of recovery from MS....but I believe it is. I believe it is proof of a brain that is healing. A brain that does not have REM (rapid eye movement) sleep, does not dream. There is research that links dreams, REM sleep and oxygenation.

"REM sleep time is strongly reduced by hypoxic and increased by hyperoxic atmosphere, in accordance with the existence of an O2 diffusion limitation. Any pathological decrease in arterial PO2 and/or O2 delivery creates a specific risk in REM sleep."
http://www.ncbi.nlm.nih.gov/pubmed/11382905

______________________________________________________

During REM sleep, there is an increase in blood flow to the limbic system and the brain stem, with circulation to these structures decreasing during non-REM sleep. As brain activity increases during REM sleep, the cerebral requirements for glucose and oxygen both increase....
Fundamentals of Sleep Technology--Butkov, Lee-Choing 2007

This research into REM and oxygenation is still in the beginning phases. I wonder if the fact of slowed perfusion through MS brains creates a need for oxygen, and that the lack of REM sleep proves this. Perhaps the low level oxygen deprivation in the brain caused by CCSVI causes what we now understand as MS spasms, myclonus, and apnea--- in a drastic attempt by the brain to rouse the body, to sit up, to take in more oxygen. My husband used to wake violently in the night, gasping for air. His spasms would jerk him awake. Before angioplasty, he never slept thru the night. He never dreamed. No wonder he was exhausted all day.

Now, I'm the one who wakes in the night-- to see him next to me, peaceful, breathing normally, and dreaming. What has changed? He used to have two malformed jugular veins which deferred to skinny, insufficient collaterals. As soon as he lay down to sleep, those jugulars created slowed perfusion. After angioplasty, he has one vein at 100% and another which is still malformed, but much better. And that is enough to allow his brain the oxygen it needs. That is enough for REM, for dreaming, for healing.

cheer

[cervocuit]

great ! it comforts me in the idea of completly stop this poison that is coffee. It’s been hard but i have reduce it to 1 cup every 3 mornings. Everyone would say that it can’t do no harm but for me there is no doubt that even this small cup of coffee affect my sleep. When i don’t take it i have more intense dreams. My bladder doesn’t wake me up between 5 and 10 times during the night. I just wet my bed (with protections) cause i’m not alert. I feel much more rest the next morning, with a clearer mind, and deep breath makes me feel good.
Furthermore, coffee causes hypoperfusion.
http://asic-cafe.org/en/system/files/15_058.pdf

What do you think about coffee ?

[1eye]

Makes perfect sense to me. You are supposed to be using jugular capacity when prone. If the jugulars are stenosed, venous return must instead use the collateral network that is normally used in upright position, when the jugular pathway has usually collapsed. In upright, I think jugulars are used as a reserve for high-pressure situations. During this time the full capacity of the jugulars is still available to the non-stenotic person, if the heart is producing enough extra pressure to keep the jugulars open. These high pressure situations usually happen at awake times.

Examining the notion that the extra capacity of the jugulars is necessary even if the collateral network is still available during sleep, a couple of things occur to me. One is that REM sleep is close to being fully awake, when we would need more blood oxygen and blood throughput. Perhaps that is part of the reason for dreaming. If myelination is more likely to occur during dreaming/REM, perhaps that fits with the idea that dreams help reinforce recently created connections for which some higher brain function is needed (though the consequent dreams do not have to have any direct reality).

Fantastic plots and characters like those found in dreams are still necessary, to give the dreams their narrative quality even during sleep. Perhaps dreams are like the kind of testing that computer programs get when all the logically possible correct and incorrect inputs are tested for each sub-function in the program, to cover all possible program execution scenarios, or even not possible ones, just to test for the correct response to all scenarios, in case a similar real event should occur in some unpredictable future context. It may be that these test runs exercise new neural connections, which have been recently myelinated.

In any case, it may be less possible to successfully perform good remyelination in hypoxic conditions. These conditions might be killing oligodendrocytes. At the same time, to produce a similar level of blood throughput, even when jugular stenosis exists, perhaps the heart must produce more pressure than it otherwise would during sleep.

If jugulars are stenotic, any reflux that does get past them (either through collaterals or the other, non-stenotic jugular), must be at a higher pressure. The result may be that it gets carried deeper into the brain.

[cheerleader]

Agree-1eye.
We know that cerebral blood flow is increased during REM sleep, and that this is the sleep during which we have dreams. Dr. Salvi and others have posited that the return of dreaming in those treated successfully for CCSVI shows an increased ability to deliver and return cerebral blood when the body is supine. It also makes sense, that since oliodendrocyte precursor cells need O2--REM sleep would be essential to brain health.

Consistently, studies have demonstrated that REM sleep is a metabolically active period for the brain. Regionally, in contrast to waking, there is a greater relative activity of limbic and paralimbic cortex. Meyer et al,[1] using the xenon inhalation method for assessing cerebral blood flow, was among the earliest to report diffuse increases in flow during REM sleep. Buchsbaum et al,[2] using the [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) method to assess brain metabolism during REM sleep, reported that the anterior cingulate cortex was the only cortical region that had greater metabolism in REM sleep in relation to waking. In a later (2001)[3] reanalysis of their data, they found that REM sleep was associated with increases in anterior cingulate, frontal, thalamus, and extrastriate cortex in relation to NREM. Maquet et al[4] reported a heterogeneous activation during REM sleep with global metabolism comparable to that of waking. Madsen et al[5] assessed cerebral blood flow during REM sleep using 99mTc-DL-hexamethylpropyleneamine. They found increased flow during REM sleep in visual association cortex and decreases in inferior frontal cortex.

http://www.medscape.com/viewarticle/503106_2

Cervocuit--I drink my daily coffee as I read your comment--I think it's probably up to the individual to assess how coffee affects their sleep cycles. It sounds like you realize coffee is not your friend. Which is a good connection to make. Jeff and I drink it in the morning, and like you, if he has it later in the day, it affects his bladder and sleep cycle. But I've been a coffee drinker since the age of 18, and I was the evil woman who got Jeff drinking it in our 20s (on a European vacation--I mixed it with hot chocolate for him.) Coffee also has many good things, like phytonutrients and antioxidants from the dark coffee bean. But one cup is enough.
cheer

[Cece]

When people are sleep deprived for a few days, they tend to have extra vivid dreams when they finally get a full night's sleep. The brain catches up on the lost REM sleep prioritizing it over other types of sleep such as deep sleep.
The vivid dreams after CCSVI treatment reminded me of this only catching up on years of lost REM sleep. We assume that it's a return to normal dreaming but it might well be beyond normal.

Very interesting to read that oligodendrocytes increase in number during REM sleep, and since oligodendrocytes make myelin, REM sleep would appear to be of great importance for MS patients and remyelination!

[1eye]

When people are sleep deprived for a few days, they tend to have extra vivid dreams when they finally get a full night's sleep. The brain catches up on the lost REM sleep prioritizing it over other types of sleep such as deep sleep.
The vivid dreams after CCSVI treatment reminded me of this only catching up on years of lost REM sleep. We assume that it's a return to normal dreaming but it might well be beyond normal.

Very interesting to read that oligodendrocytes increase in number during REM sleep, and since oligodendrocytes make myelin, REM sleep would appear to be of great importance for MS patients and remyelination!

To Cheer and others, re coffee: I remember hearing of a woman from Kenya or somewhere who was at the time the oldest person in the world. When asked how she explained it, she said she did nothing special, but that she did have one cup of coffee a day. I guess maybe Kenyan coffee is especially good for longevity.

As far as dreaming goes, I have had experiences of increased dreaming (from none to some). One was when I had had the CCSVI procedure. The other was when I was in the habit of using a CPAP machine. I do not weigh nearly as much now, so I am going in soon for another sleep study and CPAP refitting.

[cervocuit]

Sorry, this has nothing to do with the initial subject.
But on this video, they show an MRI before and after a coffee. The blood flow through your brain drop of 40%.

I guess we can find as much antioxidants in some fruits.

[1eye]

I think coffee may have a definite role. I get terrible headaches when I have been using too much and suddenly withdraw. Plus it is not a real diuretic, but it passes through you whether you want it to or not, so it may be necessary to pee sooner.

I agree completely that dreaming is part of what's wrong. I wanted to mention that one reason a collateral network plus vertebral veins plus possibly stenosed jugulars may not be sufficient, and the collateral network is required during sleep (prone position), is that there is significantly less of the journey back to lungsville that is assisted by gravity when you are lying down. I think even if you have some patency, you need as much of it as possible when lying down, including nature's adjustments like collaterals and increased venous pressure (it is not the gradient across the stenosis but how much harder the heart has to work to get enough flow during REM (which could also mean REMyelination sleep). If it never happens, on account of low O2 and glucose uptake by the brain, you never get a chance to remyelinate. Even if you fix the immune system, still you could fall behind in your remyelination. Does that sound like degeneration?

[cervocuit]

headaches during coffee withdrawal correspond to an increase of blood flow velocity and after 24 hours of complete caffeine abstinence.
http://www.ncbi.nlm.nih.gov/pubmed/9170342/
http://www.ncbi.nlm.nih.gov/pubmed/10672630/

and can appear at only 100mg/day
http://www.ncbi.nlm.nih.gov/pubmed/2262896/

What i understand of this is that a daily coffee consumer has chronic decrease of blood flow velocity.
I would add that this produce hypersecretion of gastric acids and irritate the digestive tract. And it decrease magnesium absorbtion.

[1eye]

Blood flow and velocity are different. Velocity does not take volume into account. Flow is the volume per unit of time. Velocity the linear rate of change of position per unit of time. That could be a characteristic of various size veins, and the resulting flow would be very different. I do not know whether capillaries are constricted or expanded during caffeine withdrawal, but it is a transient thing that doesn't seem to influence any of my symptoms. I do have an increase in my energy level from my morning fix. I doubt you could say a dose of 1/day cup of coffee could cause my level of disability. More likely are the tens of thousands, even millions, of black holes in my brain. Coffee has been used for thousands of years.

[David1949]

Well I had the CCSVI procedure 17 months ago. It didn't help with my worst problem, the gimpy leg. But I do dream now.

[cervocuit]

1eye
Forget about velocity. It is indeed about blood flow.
This article on caffeine and brain blood flow is very complete.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748160/
I won’t say that it can have an impact on your disability. But i think it is something to consider in the CCSVI paradigm.
Coffee is used since no more than 300 years in Europe. Which is ridiculous on the evolution scale. In comparason we eat grains and dairies since 10000 years and we are still not made to eat that.

[1eye]

Well I had the CCSVI procedure 17 months ago. It didn't help with my worst problem, the gimpy leg. But I do dream now.

I think my muscles, which have been increasingly atrophic for nine years, are going to have a tough time coming back, at age 59. It took a lot of hiking and biking to get them where they were. The nerves still don't work. I don't dream. So consider yourself to have gotten some benefit, anyway.

Forget about velocity. It is indeed about blood flow.
This article on caffeine and brain blood flow is very complete.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748160/
I won’t say that it can have an impact on your disability. But i think it is something to consider in the CCSVI paradigm.
Coffee is used since no more than 300 years in Europe. Which is ridiculous on the evolution scale. In comparison we eat grains and dairies since 10000 years and we are still not made to eat that.

Flow velocity is probably more meaningful in arteries assumed to be non-stenotic (patent).

Unless a measurement includes vessel diameter changes and pressure changes, you can't really tell what is going on. I think the real action is in venules, which caffeine shrinks, withdrawal grows, and are responsible for headache. Caffeine probably affects both veins and arteries.

In order not to starve the brain of oxygen, when caffeine shrinks venules (and capillaries?), probably there is a corresponding pressure increase. The diameter change makes the velocity increase, as decreasing the nozzle size increases water velocity from a hose. The pressure changes will also make velocity increase, but in a straight-line fashion, whereas diameter change increases or lowers it by the fourth power of the diameter. So your heart cannot compensate for a drastic change in diameter of a major vessel, as might happen if you choked an artery.

If it were a very serious problem, people would not drink coffee. Maybe all the smooth muscle exercise growing and shrinking vessels keeps it more fit, with better tone. I don't know,

The way changing vessel size affects us at night, in CCSVI, may be that the total cross-sectional area for venous neck flow is not fully compensated for, by increased number of corollaries. So when jugulars are expected to be in service, when we are lying down, there is not enough flow. We are now thinking the oxygen carried by upright veins plus jugulars when we are prone, is no longer enough to support new oligodendrocyte growth or remyelination. The oligos are more present and we do more myelin repair in REM sleep.

Most people don't drink coffee when they want to sleep. First thing in the morning is probably ok, though. You won't lose much REM sleep that way.